Geller Jordan L, Khosravi Azarmindokht, Kelly Marilyn H, Riminucci Mara, Adams John S, Collins Michael T
Clinical Research Institute, Cedars-Sinai Medical Center and the David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
J Bone Miner Res. 2007 Jun;22(6):931-7. doi: 10.1359/jbmr.070304.
Both FGF-23 and PTH inhibit renal phosphate reabsorption. We treated two patients with TIO and FGF-23-mediated hypophosphatemia with cinacalcet to test the hypothesis that medicinally induced hypoparathyroidism would decrease renal phosphate wasting. Cinacalcet treatment resulted in increased renal phosphate reabsorption, allowed for a decrease in phosphate supplementation, and showed evidence of bone healing in one of the two patients.
Tumor-induced osteomalacia (TIO) is a rare, acquired disease of renal phosphate wasting, which results in hypophosphatemia and osteomalacia. It is caused by mesenchymal tumors that produce the phosphate and vitamin D-regulating hormone, fibroblast growth factor (FGF)-23. Removal of the tumor is curative, but the tumors are often difficult to locate. Medical treatment involves high doses of oral phosphate and calcitriol, but the phosphate is often poorly tolerated and leads to diarrhea. Because PTH also promotes phosphaturia, and patients with hypoparathyroidism are hyperphosphatemic in the setting of elevated serum FGF-23, we postulated that the calcium-sensing receptor agonist, cinacalcet, which can induce hypoparathyroidism, would be an effective adjuvant in the treatment of TIO.
Two subjects with presumed TIO in whom the tumor was not located after extensive testing and who did not tolerate medical therapy with phosphorus and calcitriol were treated with cinacalcet.
Neither treatment with phosphorus nor combined treatment with phosphorus and calcitriol had an effect on serum FGF-23 levels. Treatment with cinacalcet resulted in increased renal phosphate reabsorption and serum phosphorus and allowed for a decrease in phosphate supplementation to a dose that was tolerated. On this regimen, one patient showed significant bone healing as shown by resolution of activity on bone scan and lack of osteomalacia as assessed by histomorphometry.
These data show that medically induced hypoparathyroidism with cinacalcet is a therapeutic option for disorders of FGF-23-mediated hypophosphatemia and that, in the absence of PTH, the phosphaturic effect of FGF-23 is decreased.
成纤维细胞生长因子23（FGF - 23）和甲状旁腺激素（PTH）均抑制肾脏对磷酸盐的重吸收。我们用西那卡塞治疗了两名患有肿瘤性骨软化症（TIO）和FGF - 23介导的低磷血症的患者，以检验药物性诱导甲状旁腺功能减退会减少肾脏磷酸盐流失这一假设。西那卡塞治疗导致肾脏对磷酸盐的重吸收增加，允许减少磷酸盐补充量，并且在两名患者中的一名显示出骨愈合的迹象。
肿瘤诱导的骨软化症（TIO）是一种罕见的、后天性的肾脏磷酸盐流失疾病，导致低磷血症和骨软化症。它由产生磷酸盐和维生素D调节激素——成纤维细胞生长因子（FGF）- 23的间充质肿瘤引起。切除肿瘤可治愈，但肿瘤往往难以定位。药物治疗包括高剂量口服磷酸盐和骨化三醇，但磷酸盐通常耐受性差并导致腹泻。由于PTH也促进尿磷排泄，并且甲状旁腺功能减退患者在血清FGF - 23升高的情况下会出现高磷血症，我们推测可诱导甲状旁腺功能减退的钙敏感受体激动剂西那卡塞在TIO治疗中会是一种有效的辅助药物。
两名推测患有TIO的受试者，在经过广泛检查后未找到肿瘤且不能耐受磷酸盐和骨化三醇的药物治疗，接受了西那卡塞治疗。
单独使用磷酸盐治疗或磷酸盐与骨化三醇联合治疗均对血清FGF - 23水平无影响。西那卡塞治疗导致肾脏对磷酸盐的重吸收增加以及血清磷升高，并允许将磷酸盐补充量减少至可耐受剂量。在此治疗方案下，一名患者显示出明显的骨愈合，表现为骨扫描活动消退，并且通过组织形态计量学评估无骨软化症。
这些数据表明，用西那卡塞药物性诱导甲状旁腺功能减退是FGF - 23介导的低磷血症疾病的一种治疗选择，并且在没有PTH的情况下，FGF - 23的促尿磷排泄作用会降低。
